The parasympathetic nervous system is of central importance in the regulation of airway caliber. Specific antigen induces bronchoconstriction which is dependent on vagally mediated reflex pathways in anesthetized, allergic dogs. Vagal reflex pathways are also important in the regulation of ventilation: Selective blockade of vagal reflexes shows that slowly adapting (stretch reflex) receptors inhibit, while irritant receptors stimulate breathing. The interaction between these parasympathetic pathways may integrate breathing patterns with bronchomotor tone. Other in vitro studies indicate that parasympathetic agonists facilitate antigen- induced release of histamine and other chemical mediators. These results suggest that parasympathetic nervous mechanisms may interact with biochemical mechanisms in regulating the response to inhaled antigen in the intact, allergic animal. Since anesthesia can alter respiratory mechanics and vagal control of respiration, I have examined the role of parasympathetic mechanisms in regulating respiration in trained, conscious, exercising dogs. I have carried out a series of preliminary experiments evaluating the effect of vagal blockade on the respiratory response to inhaled histamine in these animals. Vagal blockade completely abolished the increased ventilation although not completely inhibiting the bronchoconstriction induced by histamine. This suggests that pulmonary receptors with afferent vagal pathways mediate hyperpnea induced by histamine. In this project I plan to evaluate the role of vagal and biochemical mechanisms in regulation of respiratory and bronchomotor responses to inhaled antigen in the conscious, allergic, exercising dog. Vagal mechanisms will be evaluated by cooling cervical vagal loops and by local anesthetic aerosols; biochemical mechanisms will be studied by measuring release of histamine and other mediators with and without vagal cooling as well as following mediator depletion. These studies will permit assessment of the relative importance of parasympathetic and biochemical mechanisms in regulating the respiratory responses in experimental asthma.